ABSTRACT
Background: Recent studies highlight the dynamic nature of virus-host interaction during SARS-CoV-2 infection, raising intriguing questions about the role and timing of interferon (IFN) responses. In fact, SARS-CoV-2 delays/antagonizes Type-I, and to a definitely lesser extent, Type II-IFNs. While paving the way for potential antiviral therapies based on immune activation, the molecular mechanisms linking different IFN pathways to SARS-CoV-2 susceptibility remain to be elucidated. The present study investigates the role of Type-I &-II IFNs in SARS-CoV-2 replication in human lung cells, with a focus on molecular pathways related with innate and adaptive immunity. Methods: Human lung carcinoma cells (CaLu3) were pretreated with IFN-α,-β or-γ (from 1 to 1000 U/mL), O.N. Cells were infected with SARS-CoV-2 (MOI 0.05) for 3h, and IFNs were added during infection. In another set of experiments, IFNs were added only p.i. Supernatants were harvested at 24 and 48h p.i. to assess viral replication by RT-qPCR, and to quantify the levels of cytokines/chemokines through Multiplex assay. At 48h post-infection, cells were collected and RNA was retrotranscribed to investigate a variety of transcriptional targets. Cell viability was assessed by MTT. Results are presented as the average of the relative expression units to the GAPDH gene, calculated by the 2-ΔΔCt equation. Statistical analyses were performed through the Student t-test. Results: Pretreatment with both Type-I &-II IFNs dramatically reduces SARS-CoV-2 replication in the absence of cell toxicity. Such an effect is maintained, though at a lower magnitude, when IFNs are added only p.i. The antireplicative effects of Type-I &-II IFNs are associated with both convergent and divergent mechanisms. Both Types decrease the expression and/or protein levels of most pro-inflammatory mediators while augmenting anti-inflammatory and anti-apoptotic factors. Surprisingly, IFN-γ shows the strongest effect in potentiating antiviral effectors besides boosting adaptive immunity pathways. Remarkably, a convergent effect of both IFN Types is observed upon the expression of genes associated with DA activity, including DA receptors (D1-D5) and the DA transporter (DAT), which are dramatically altered by SARS-CoV-2. Conclusion: Both Type-I &-II IFNs halt SARS-CoV-2 replication by acting through complementary mechanisms. Their effects also disclose a potential role for DA activity, and neuromodulators in general, in host immunity during SARS-CoV-2 infection in pulmonary cells.
ABSTRACT
With the advent of the COVID19 pandemic, all patients in our heart failure clinic (HFC) were assessed by telephone instead of the scheduled visit, thus showing the need for an additional remote monitoring system. Telecardiology (TC) is already a well-established practice in our clinic in patients with devices. From a joint collaboration project of APSS, FBK and Trentino salute 4.0, an APP was developed, available on the Play Store: TreC Cardiologia. The project started with Beta Test on 29 June 2020. The APP was initially given to patients already followed by the TC clinic and subsequently to those followed by the HFC or discharged with a diagnosis of heart failure (HF) . The APP allows you to: 1) monitor the progress of some customizable clinical parameters;2) interface with our clinic via chat to send text messages to communicate any symptoms and send photographic material;3) perform scheduled or on-demand video calls;4) view the therapy;5) set reminders for the patient on certain actions to be performed, fill forms about his health conditions;6) in the future, patients will be able to access educational material on their pathology. The project also includes a dedicated nurse who takes care of the management of the patient with APP from administration onwards, favoring his empowerment, reporting elements of destabilization to the referring doctor with subsequent decisions (video call, in-office visit, hospitalization). As of 31/12/2020 the APP was given to 66 patients. Since March 2020, HFC patients are still followed up with a phone call and/or an in-office visit, according to clinical trend. The use of the APP and the collection of data relating to efficacy and criticality have begun.The use of additional instrumentation to be provided to the patient is being evaluated. The literature that emerged from the COVID19 pandemic has confirmed the role of telemedicine in optimizing management at home in patients with HF. The new readily available technologies (e.g. smartphone with the possibility of video call) also allow you to maintain eye contact with the patient, taking on both clinical and psychological value, highlighting destabilization in time and also being reassuring about the pandemic. The epidemiology of HF and the ongoing pandemic suggest that technology will have to increasingly support the management of these patients.